Literature DB >> 10733472

Differential Th1/Th2 cytokine patterns in chronic arthritis: interferon gamma is highly expressed in synovium of rheumatoid arthritis compared with seronegative spondyloarthropathies.

J D Cañete1, S E Martínez, J Farrés, R Sanmartí, M Blay, A Gómez, G Salvador, J Muñoz-Gómez.   

Abstract

OBJECTIVE: To investigate possible differences in Th1 and Th2 cytokine mRNA expression in the synovial tissue (ST) of patients with rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA) with diagnostic and/or pathogenic interest.
METHODS: Eleven RA patients and 14 SpA patients (10 with undifferentiated spondyloarthropathy (USpA), two with ankylosing spondylitis (AS) and two with psoriatic arthritis (PsA)) were included. Th1 (interferon gamma, interleukin 2) and Th2 (interleukin 4, interleukin 5 and interleukin 10) cytokine mRNA levels from arthritic knee ST were quantified by using an optimised polymerase chain reaction method with a computerised analysis system. Protein levels of proinflammatory cytokines (interleukin 1, tumour necrosis factor alpha and interleukin 6) in synovial fluid were quantified with a specific ELISA test.
RESULTS: Th1 cytokines were detected in all of RA ST samples in contrast with 58% (interferon gamma) and 71% (interleukin 2) of SpA samples. Th2 cytokines were expressed in 90% of RA ST samples, but the findings in SpA were interleukin 10 in 90%, interleukin 4 in 60% and interleukin 5 in 40% of ST samples. However, when the mRNA levels of each cytokine were quantified and corrected for T cell mRNA levels, only interferon gamma levels were significantly higher in RA than in SpA (p<0.003). Thus, the Th1/Th2 cytokine ratio in RA was fivefold that of SpA. Synovial fluid interleukin 1beta concentrations were higher in RA than in SpA (p<0. 05); there were also higher synovial fluid levels of tumour necrosis factor alpha in RA than in SpA, but without statistical significance.
CONCLUSION: This study has detected both Th1 and Th2 cytokine gene expression in ST from RA and SpA patients. Synovium interferon gamma mRNA levels and SF interleukin 1beta protein levels were significantly higher in RA than in SpA, so reflecting the known proinflammatory activity of interferon gamma through macrophage activation. Thus, the Th1 (interferon gamma)/Th2 (interleukin 4) ratio is significantly higher in RA than in SpA ST. These data confirm previous studies on ST Th1/Th2 balance in RA and extend previous work in comparing ST RA with subgroups of SpA distinct of ReA.

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Year:  2000        PMID: 10733472      PMCID: PMC1753106          DOI: 10.1136/ard.59.4.263

Source DB:  PubMed          Journal:  Ann Rheum Dis        ISSN: 0003-4967            Impact factor:   19.103


  43 in total

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Authors:  G Cunnane; B Bresnihan; O FitzGerald
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Review 2.  Th1/Th2 cytokine balance in arthritis.

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Review 3.  Functional diversity of helper T lymphocytes.

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5.  Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein.

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Journal:  N Engl J Med       Date:  1997-07-17       Impact factor: 91.245

Review 6.  Role of cytokines in rheumatoid arthritis.

Authors:  M Feldmann; F M Brennan; R N Maini
Journal:  Annu Rev Immunol       Date:  1996       Impact factor: 28.527

7.  In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from patients in early stages of rheumatoid, reactive, and undifferentiated arthritis.

Authors:  S Kotake; H R Schumacher; C H Yarboro; T K Arayssi; J A Pando; K S Kanik; M F Gourley; J H Klippel; R L Wilder
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8.  Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors.

Authors:  J Braun; M Bollow; G Remlinger; U Eggens; M Rudwaleit; A Distler; J Sieper
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9.  Crucial role of interleukin-10/interleukin-12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis.

Authors:  Z Yin; J Braun; L Neure; P Wu; L Liu; U Eggens; J Sieper
Journal:  Arthritis Rheum       Date:  1997-10

10.  Comparative cytokine gene expression in synovial tissue of early rheumatoid arthritis and seronegative spondyloarthropathies.

Authors:  J D Cañete; J Llena; A Collado; R Sanmartí; A Gayá; J Gratacós; M Blay; J Muñoz-Gómez
Journal:  Br J Rheumatol       Date:  1997-01
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  54 in total

Review 1.  Disease mechanisms in psoriasis and psoriatic arthritis.

Authors:  P Costello; O FitzGerald
Journal:  Curr Rheumatol Rep       Date:  2001-10       Impact factor: 4.592

Review 2.  Th2 mediated regulation in RA and the spondyloarthropathies.

Authors:  J A G van Roon; J W J Bijlsma
Journal:  Ann Rheum Dis       Date:  2002-11       Impact factor: 19.103

Review 3.  The transition of acute to chronic bowel inflammation in spondyloarthritis.

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4.  Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis.

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5.  Preferential type 1 chemokine receptors and cytokine production of CD28- T cells in ankylosing spondylitis.

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6.  Gamma interferon positively modulates Actinobacillus actinomycetemcomitans-specific RANKL+ CD4+ Th-cell-mediated alveolar bone destruction in vivo.

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Review 7.  Pathogenesis of spondyloarthritis: insights from synovial membrane studies.

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8.  LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and microbial infection.

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9.  All-trans-retinoic acid suppresses interferon-gamma and tumor necrosis factor-alpha; a possible therapeutic agent for rheumatoid arthritis.

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10.  IFN-gamma regulates the requirement for IL-17 in proteoglycan-induced arthritis.

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